Inflammation is the foundation for cancer and degenerative/autoimmune diseases. Small changes in diet and exercise, e.g. omega-3 oils, vitamin D, low starch, and maintaining muscle mass, can dramatically alter predisposition to disease and aging, and minimize the negative impact of genetic risks. Based on my experience in biological research, I am trying to explain how the anti-inflammatory diet and lifestyle combat disease. 190 more articles at http://coolinginflammation.blogspot.com

Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:

Sunday, February 16, 2014

...All 190 posts...I am definitely not a bandwagon kind of guy (except maybe in the case of fecal transplants.)So embracing evil, high-glycemic starch as a medicinal godsend was tough.As a biochemist raised on structural analysis of carbohydrates, the idea of starch as a mixture of linear amylose and branched amylopectin, was straightforward.Amylase in saliva and pancreatic solutions digests the linear alpha,1-4,glucan stretches and pullulanase (bacterial) degrades the alpha,1-6, glucan branch points.But this suggests that starch should be digested before it gets to the colon and most of the gut flora.This ignores the spirals of amylose that resist amylase digestion, i.e. resistant starch (RS), and that lead to the puzzling role of RS as a special food for gut flora and a health panacea.

Why is resistant starch, RS, difficult to digest and terrific for gut flora?

There are several conceptual difficulties to understanding why RS is Real Special:

Polysaccharides are not all simple linear chains of sugars, e.g. they branch (amylopectin) or form helices (RS, amylose).

Sugars and polysaccharides have hydrophobic patches.They are amphipathic like soap.

Amylose (RS) forms a spiral with a hydrophobic surface of each sugar facing inward to make a hydrophobic core and hydrophobic patches on the outer surface that structures water to hold the spirals together.The same principle holds together the double helices of DNA around a central hydrophobic core of stacked base pairs.

Polysaccharides (soluble fiber) are made of many different sugars, e.g. glucans, mannans, xylans, galacturonans, etc.

Starch is enzymatically hydrolyzed to glucose, which most gut flora can ferment.Other sugars from other polysaccharides (e.g. pectin, polygalacturonan) must first be converted to glucose for fermentation.

Several hundred bacterial enzymes of the gut flora are required to digest the complex soluble fibers of food plants in a typical diet.Resistant starch requires two.

Food intolerances (also mistakenly called food allergies) result from missing bacteria and their enzymes to fully digest soluble fibers.

Novel soluble fibers or sugars are used as laxatives, and they lose their loosening impact as your gut flora adapts to digest the new fiber.Normal, softened stools are half bacteria.

Amylose spirals are used as a storage form of glucose in seeds, potatoes, roots, etc., because enzymes can’t attack their glycosidic bonds to hydrolyze the starch into amylodextrins and glucose.

Bacteria digest amylose by attaching the spirals to their cell walls and using wall-bound enzymes to tear the amylose apart.It's like the different requirements of a wood chipper (pancreatic amylase) versus a man with a chain saw (bacterial amylase).

The spirals of RS melt during cooking and become susceptible to gut amylase.Melted amylose can sometimes slowly reform enzyme-resistant spirals, RS, when chilled.Al dente or chilled pasta has more RS and raises blood sugar less than soft pasta.

Resistant Starch, a Unique Soluble Fiber

Humans only produce enzymes (amylases) to degrade one of the hundreds of plant polysaccharides, linear starch. RS is not degraded by human amylases and, as with other soluble fibers, it is degraded by bacterial enzymes in the colon and is fermented to short chain fatty acids. The difference is that the glucose released from hydrolysis of RS is used directly by common gut bacteria, whereas the other sugars released from other soluble fibers require enzymes produced by particular species of bacteria to be converted first to glucose. RS is a unique form of starch and a unique soluble fiber.

Short Chain Fatty Acids and Immune Cells Required for Health

Gut flora eat soluble fiber and produce short chain fatty acids, e.g. acetic, butyric, propionic acids, that feed the cells of the intestines and lower inflammation. The development of both the aggressive and the suppressive (Tregs) halves of the immune system requires healthy gut bacteria. The bacteria that digest RS, for example, are Clostridia (see EM right, note bacterium dissolving its way into the grain of RS), the type of gut flora that also stimulates Tregs and prevents autoimmunity. Thus, the beneficial impact of dietary RS results from feeding gut flora. Most people already support gut flora that can utilize RS, so most people benefit from RS in their diet. Some people have severely damaged gut flora, dysbiosis and constipation, and they may need to eat live, fermented foods (not just dairy probiotics) to recruit enough new bacteria to benefit from RS. Other healthy people may already have healthy gut flora that can exploit all of the soluble fiber in a compatible healthy diet, and need no further enhancement of their health by RS. Health always requires gut flora complementary to diet and each change in diet requires accommodation by corresponding changes in gut flora. Some changes in diet may require new species of gut bacteria.

Does Altered RS in Modern Bread Explain Gluten Intolerance?

The RS remaining in today’s superfine flour that is rapidly cooked into bread and other foods, may be very different from previous generations. Traditional hydration and exposure to fermenting microorganisms may have produced breads with higher levels of RS that contributed to healthier gut flora. Healthier gut flora would in turn produce less intestinal inflammation and a reduced response to gluten.

Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer.METHODS:

In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was done with a block size of 16. Post-intervention, patients entered into double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint for this analysis was development of colorectal cancer in participants randomly assigned to resistant starch or resistant-starch placebo with both intention-to-treat and per-protocol analyses. This study is registered, ISRCTN 59521990.FINDINGS:

Resistant starch had no detectable effect on cancer development in carriers of hereditary colorectal cancer. Dietary supplementation with resistant starch does not emulate the apparently protective effect of diets rich in dietary fibre against colorectal cancer.FUNDING:

It's been awhile since I commented, but glad to see your back and active. Isn't immune response also contingent on the type of gut flora itself, I.e. The immune system learns to respond based upon interaction with the bacteria in the colon? RS would simply be feeding the gut flora, right? Also, why do you think anecdotes for resistant starch are talking about better quality sleep? Is inflammation messing up sleep, with this new sleep indicative of less inflammation?

Dr. J,Thanks for the background on RS and cancer.I wouldn't expect RS to reduce cancer. It seems to foster the growth of Clostridia, which I associate with enhancing Tregs. That also means butyrate production and lowered inflammation, which should reduce cancer, but the Tregs suggest to me reduced immunological aggression and cancer tolerance.The bottom line is that RS will be a wash for cancer, but should be useful along with other soluble fiber in cancer therapy.

Hi Asim,Nice to hear from you again.I would guess that by lowering inflammation, RS also enhances vitD production and so contributes to sleep. It would be interesting to see if the epidemic of vitD deficiency yields to RS. I don't know enough about melatonin to go there.

I'm a celiac with ongoing inflammation so I'm trying the SCD, which is, for all intents and purposes, completely anti-starch. The argument (I'm sure you know this) is that simplifying the diet to monosaccharides will eliminate overgrowth of harmful bacteria. Any thoughts? Opinion on the SCD in general?

First is a simple one, if RS mediates its benefits through an immune interaction through butyrate, why not just take butyrate itself? Especially if you are eating fermented foods and an otherwise healthy diet that provides a "good" microbiome composition? This is a question I have seen brought up several times in regards to RS, but then never really addressed.

Second, you mentioned that RS is digested by clostridia, a bacteria specifically involved in Treg activity and autoimmunity. I recently attended a talk by Dr. Dingding An from Harvard where she discussed her work on B. fragilis derived sphignolipids, and the role they play in early life development of host immunity (Here is her most recent publication, however her talk covered all of her postdoc work http://www.ncbi.nlm.nih.gov/pubmed/24439373), it was very interesting, and I see some parallels between her talk and your post. My question is could we be seeing a similar situation here, where if we properly develop the immune system in early life with things like RS, or just not destroy it with crap nutrition, are we not going to need all these "hacks" later in life?

I understand the role of the microbiome in modulating host immunity, however, I feel that it is just that, a modulator. I struggle to see how people claim that things like RS are these be all end all strategies for curing all of life's ailments. I also understand that it is not possible for us to go back in time and take all the proper steps to develop our immune systems perfectly from the get go, however I feel that not taking into account early life immune development is a large confounder in a lot of this research. Any and all of your opinions on this would be greatly appreciated.

Thank you for another interesting post. I have the same question your commenter Al Towers has, if the real issue is getting SCFA into the gut why not just take butyrate and others? Wouldn't that be beneficial to everyone but especially those that don't have the right bacteria to break down the RS? According to:

http://www.nature.com/ismej/journal/v6/n8/full/ismej20124a.html

If r. bromii is not present you will not break down the RS.

Also, I've looked over at Dr. Eades and some others and apparently the science has not convinced them. Eades calls RS an anti-nutrient. Now to be fair this was back in 2008 perhaps he has changed his mind.

My point being I have limited ability to look at the original science and interpret it myself so I look to you and other sites to help me with that. But what do you do when the sites you use for guidance don't agree?

Asim - I would say that high inflammation, of any kind, causes cortisol to rise in response, and chronic inflammation can cause the adrenal glands to respond with higher and higher levels of cortisol, eventually disrupting sleep. Since cortisol levels should rise and fall in a predictable pattern in a healthy individual with little or no inflammation, chronic inflammation would cause cortisol to be high all of the time, and the longer the inflammation lasts, the higher cortisol levels will rise. This probably partially accounts for adrenal insufficiency in people with autoimmune issues.

@Al Towers: My understanding is that ingested butyrate doesn't make it through the stomach to the large intestine. Or if it does, it only makes it to the proximal end. Butyrate created by the gut bacteria using RS as food floods the entire LI.

@Asim: One possible mechanism for improved sleep is that mitochondria can use SCFAs for energy, reducing low blood sugar during sleep. The other is increased production of B6, and/or increased production of various neurotransmitters. But the improved sleep is one of the more common anecdotal reports, so it's going to be interesting to find out what's doing that. I'm semi-convinced that the more vivid dreaming also reported by many has to do with B6, as you can take supplemental B6 before bed to induce vivid or lucid dreams (according to some sources).

@ dr j. I wouldn't think that just adding RS to an ordinary SAD diet would make a difference. It might however need to be part of a whole package that supplies key bacteria plus possibly cutting out some SAD processed foods.

@ Al. As regards taking butyrate directly. This is an issue commented on a range of blogs I've read but I'm not a biochemist nor an expert so am only reporting what I've read. Apparently directly eaten butyrate is digested before it gets to the lower gut where it is actually needed by the immune system. Therefore one needs both the appropriate bacteria plus the food for these bacteria so a direct butyrate source doesn't give us the effect we are looking for.

And I don't know of any serious health researcher or health explorer who believes RS is the be all and end all for health. It always comes as part of a package.

@ Nils "What are your thoughts on Clostridium difficile, could this be made worse by ingesting lots of RS?"Maybe this is less of a problem in people who are vitamin d replete.Here is an example of one of several papers showing low Vitamin d status is associated with increased C Diff severityVitamin D Status and Severity of Clostridium difficile Infections"

1. Ebringer and Wilson C. The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis. Clinical Rheumatology 1996; 15 Suppl. 1, 61-65.

2. Ebringer A. Ankylosing spondylitis is caused by Klebsiella.

If one reacts horribly to starches with this condition, is a complete avoidance of them(starches) going to cause even further gut disruption? Would one form of starch be easier to introduce than others?

I forgot to add in the line from the abstract- " Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs."

So one can speculate- promote the ecology of microbes that ferment substrates to eventually stimulate the expression of IL-10.

Dr. J,That is an interesting picture of gut flora, inflammation and various stages of cancer. It is interesting that RS gives a different pattern than other soluble fiber and that the fibers and flora are synergistic in suppressing cancer. It seems that cancer is blocked by a fully functional immune system developed by a diverse gut flora.

Antibiotics paired with the lack of a medical approach to repair of gut flora leads to chronic treatment and no cures.

About the idea that dietary butyrate is used up and doesn't reach the parts you want it to; this may be true of butyrate supplements, but isn't butyrate in foods like butter mostly in triglyceride form (unless it's completely rancid), requiring the action of lipase before the butyric acid can begin to be absorbed?It may not reach the colon in appreciable amounts, but it will reach the liver, which is one of the places its benefits will be felt.

I was wondering, what about ingesting a small amount of clay for probiotic bacteria? When I've researched betonite clay, the blogosphere insists that pre-modern cultures all ate a tiny amount of clay with their meals. The assumption is that clay adsorbs toxins and bad bacteria. Is it possible that instead, the clay is alkaline and hosts bacteria good for the human gut?

Hi. Do you know anything about incretines causing reactive hypoglycemia? I'm 21 years old and I've been dealing with severe reactive hypoglycemia that started 2 years ago... I've done many tests and just until recently doctors found out the problem it's in GLP-1 and GIP (I guess I'm writting it correctly). I still don't have the results in my hands but after talking to my doctor today they are still investigating and think it's something rare cause they never heard of anything like that. But reactive hypoglycemia/hypoglycemia was never a real thing for docs here so I don't know where I stand. If you could give me your insight or recommend someone that I can email about this I would be very very thankful. I live in Portugal.

@ Maria - my reactive hypoglycemia is caused by adrenal fatigue. I never had it before my adrenals tanked on me last year. Have you had your cortisol levels tested? Are doctors aware of adrenal insufficiency where you are?

I'm someone with chronic constipation. I am starting supplementing with potato starch, and understand from your posts and others that I am probably lacking the bacteria to eat it. So, I've purchased a probiotic called Ultimate Flora which contains several bifidobacterium strains along with lactobacillus strains. It claims to contain 150 billion cultures per capsule. Thoughts? Can taking too much of this be harmful?

I tried Resistant Starch and it was terrible for me. I have an overgrowth of Klebsiella and cannot eat most starches, the RS exacerbated my symptoms. Wish I could tolerate it, as I'm impressed by the success stories. Wondering if I can starve out the Klebsiella and then try RS again.

Thank you for your wonderful blog. I have a question regarding the mechanisms of SCFA's created by resistant starch. Are they broken down by enzymes in the same way, or with the same enzymes as foods containing SCFA's? I ask because I have a Fatty Acid Oxidation Disorder called short chain acyl-CoA dehydrogenase deficiency. I do not have all of the enzymes needed to break down SCFA's. One of the main protocols for all FOD's is low fat, high carb diet. No one mentions limiting prebiotics nor resistant starch. Before I learned I had an FOD, I took PS as RS and it cured my constipation without changing my Sibo breath test numbers. Can you help determine if prebiotics and/or RS is dangerous for someone with a limited ability to break down SCFA's? Thanks in advance!

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About Me

I grew up in San Diego and did my PhD in Molecular, Cellular and Developmental Biology (U. Colo. Boulder). I subsequently held postdoctoral research positions at the Swedish Forest Products Research Laboratories, Stockholm, U. Missouri -Colombia and Kansas State U. I was an assistant professor in the Cell and Developmental Biology Department at Harvard University, and an associate professor and Director of the Genetic Engineering Program at Cedar Crest College in Allentown, PA. I joined the faculty at the College of Idaho in 1991 and in 1997-98 I spent a six-month sabbatical at the National University of Singapore. Most recently I have focused on the role of heparin in inflammation and disease.